Circulating exosomal CPNE3 as a diagnostic and prognostic biomarker for colorectal cancer

Sun, Bo; Li, Yiming; Zhou, Yiming; Ng, Tien Khee; Zhao, Chao; Gan, Qiaoqiang; Gu, Xiaodong; Xiang, Jianbin

doi:10.1002/jcp.26936

Cited by 109 publications

(76 citation statements)

References 25 publications

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“…TRIM3 plays a role as tumor inhibition in gastric cancer, and TRIM3 knockdown can promote the growth and metastasis of gastric cancer by regulating stem cell factor and EMT regulator. By surveying the clinical studies on protein markers in exosome, most studies detected the levels of protein expression in total [11] up-regulation CD147 [12] up-regulation pancreatic ductal adenocarcinoma GPC-1 [13,14] up-regulation Gastric cancer HER-2/neu, EMMPRIN, MAGE-1, C-MET [15] up-regulation TRIM3 [16] down-regulation Prostate cancer PSA [17] up-regulation ephrinA2 [18] up-regulation survivin [19] up-regulation melanoma (phospho)Met [20] up-regulation caveolin-1 [21] up-regulation…”

Section: Protein Expression Levelmentioning

confidence: 99%

Progress in exosome associated tumor markers and their detection methods

Shen

He³

et al. 2020

Mol Biomed

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Exosomes are secreted by cells and are widely present in body fluids. Exosomes contain various molecular constituents of their cells of origin such as proteins, mRNA, miRNAs, DNA, lipid and glycans which are very similar as the content in tumor cells. These contents play an important role in various stages of tumor development, and make the tumor-derived exosome as a hot and emerging biomarker for various cancers diagnosis and management in non-invasive manner. The present problems of exosome isolation and detection hinder the application of exosomes. With the development of exosome isolation and detection technology, the contents of exosomes can be exploited for early cancer diagnosis. This review summarizes the recent progress on exosomeassociated tumor biomarkers and some new technologies for exosome isolation and detection. Furthermore, we have also discussed the future development direction in exosome analysis methods. Development on exosome tumor markers Extracellular vesicle (EV) includes exosomes, microvesicles and apoptotic bodies. These vesicles have different size and biogenesis. Exosomes are complex 20-100 nm vesicles and generate in a way that intracellular multivesicular bodies (MVBs) containing intraluminal vesicles (ILVs) fuse with the plasma membrane [1]. Larger vesicles, microvesicles (100 nm-1 μm) and apoptotic bodies (1-5 μm), are released directly from the budding and fission of the plasma membrane [2]. In the past decades, researchers have become increasingly interested in the role of EVs, especially exosomes, in diseases. Exosomes contain various molecular constituents of their cell of origin such as proteins, RNAs, DNA, lipid glycans. Therefore, tumor-derived exosomes could tell the physiological and pathological states of parent tumor cells, and emerged to be a hot cancer biomarker in liquid biopsy field [3]. Given the rich molecular composition of exosomes and easy availability of liquid biopsy sample, many researchers [4] are pursuing to develop non-invasive diagnostic methods with higher sensitivity and specificity based on exosome, which has very high potential to help early diagnosis, treatment evaluation, and prognostic analysis of the disease. In this section, we have summarized the application of exosomes in tumor diagnosis based on its amount and molecular compositions. Level of exosomes in tumor diagnosis Studies show that the level of exosomes in plasma was significantly higher in cancers (such as ovarian cancer [5] and non-small-cell-lung cancer [6]) patients than that of healthy controls [7]. Therefore, many researchers hypothesize that levels of exosome in bodily fluid can serve as a potential diagnostic biomarker in cancer patients. Logozzi et al. [8] investigated the amount of

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Section: Protein Expression Levelmentioning

confidence: 99%

Progress in exosome associated tumor markers and their detection methods

Shen

He³

et al. 2020

Mol Biomed

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“…cancer associated proteins inside cancer-derived EVs has led to the identification of several potential disease biomarkers such as CPNE3 in colorectal cancer EVs 25 , miR-451a in non-small cell lung cancer EVs 26 , and miR-451a in pancreatic ductal adenocarcinoma EVs 27 , all of which are associated with poor disease-free survival.…”

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confidence: 99%

A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum

Brennan

Martin²,

Fitzgerald

et al. 2020

Sci Rep

615

550

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extracellular vesicles (eVs) are nano-sized vesicles containing nucleic acid and protein cargo that are released from a multitude of cell types and have gained significant interest as potential diagnostic biomarkers. Human serum is a rich source of readily accessible eVs; however, the separation of eVs from serum proteins and non-eV lipid particles represents a considerable challenge. in this study, we compared the most commonly used isolation techniques, either alone or in combination, for the isolation of EVs from 200 µl of human serum and their separation from non-eV protein and lipid particles present in serum. the size and yield of particles isolated by each method was determined by nanoparticle tracking analysis, with the variation in particle size distribution being used to determine the relative impact of lipoproteins and protein aggregates on the isolated EV population. Purification of eVs from soluble protein was determined by calculating the ratio of eV particle count to protein concentration. finally, lipoprotein particles co-isolated with eVs was determined by Western blot analysis of lipoprotein markers ApoB and Apoe. overall, this study reveals that the choice of eV isolation procedure significantly impacts EV yield from human serum, together with the presence of lipoprotein and protein contaminants. Extracellular vesicles (EVs) were originally identified in reticulocytes as a means of disposing of obsolete membrane proteins such as α4β1 and transferrin receptor during reticulocyte maturation 1-3 , and have since been shown to participate in cell-cell signalling via transfer of proteins, nucleic acids and metabolites 4-6. EVs have been identified in a diverse range of human biofluids including serum, plasma, urine, saliva, breast milk, amniotic fluid, ascites fluid, cerebrospinal fluid and bile 7,8. These EVs are classified into three groups; exosomes, microvesicles and apoptotic bodies depending on their size, biogenesis and method of cellular release. Microvesicles and apoptotic bodies generally range from 100 to 1000 nm and 1-4 µm respectively, and are formed by budding from the plasma membrane 4,9. In contrast, exosomes have a diameter of 30-150 nm and are formed by inward budding of the late endosome lumen to form a multivesicular body (MVB) that is secreted by fusion with the plasma membrane 10. The overlap in exosome and microvesicle size (100-150 nm) and density (1.08-1.19 g/ml) makes it difficult to distinguish the two groups and as a result exosomes are often defined by their content of endosome-associated proteins including tetraspanins CD9, CD63, and CD81. However, since microvesicles from haematopoietic cells are also enriched for endosomal proteins such as CD63 and CD81 11 exosomes and microvesicles <150 nm are collectively referred to as small extracellular vesicles (sEVs) 12. EV secretion has been shown to be elevated in response to inflammation 13 , hypoxia 14,15 and an acidic microenvironment 16,17 and is associated with human diseases such as cancer, where secretion levels have b...

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“…Three conclusions come from the study published by Xiao et al [ 67 ]: (1) CK19, TAG72 and CA125 were shown to be specific antigens for CRC exosomes; (2) high levels of exosomal TAG72 could specify the group of patients resistant to 5-fluorouracil (5-FU); and (3) CA125-rich small EVs could serve as a metastatic biomarker [ 67 ]. Sun et al [ 68 ] presented a comparatively small number of CRC patients with increased levels of blood exosomal copine 3 (CPNE3). In this study [ 68 ], the group of patients who were diagnosed with advanced cancer stages and distant metastasis had elevated levels of exosomal CPNE3.…”

Section: Evs In Gastrointestinal (Gi) and Liver Cancer Managementmentioning

confidence: 99%

“…Sun et al [ 68 ] presented a comparatively small number of CRC patients with increased levels of blood exosomal copine 3 (CPNE3). In this study [ 68 ], the group of patients who were diagnosed with advanced cancer stages and distant metastasis had elevated levels of exosomal CPNE3. Moreover, the combined exosomal CPNE3/carcinoembryonic antigen (CEA) test appears to be a suitable tool distinguishing CRC cases from healthy controls [ 68 ].…”

Section: Evs In Gastrointestinal (Gi) and Liver Cancer Managementmentioning

confidence: 99%

“…In this study [ 68 ], the group of patients who were diagnosed with advanced cancer stages and distant metastasis had elevated levels of exosomal CPNE3. Moreover, the combined exosomal CPNE3/carcinoembryonic antigen (CEA) test appears to be a suitable tool distinguishing CRC cases from healthy controls [ 68 ]. Prior work had also established that increased levels of blood exosomes were associated with shorter overall survival of CRC patients [ 69 ].…”

Section: Evs In Gastrointestinal (Gi) and Liver Cancer Managementmentioning

confidence: 99%

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EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

Słomka

Mocan

Wang

et al. 2020

Cancers

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For more than a decade, extracellular vesicles (EVs) have been in focus of science. Once thought to be an efficient way to eliminate undesirable cell content, EVs are now well-accepted as being an important alternative to cytokines and chemokines in cell-to-cell communication route. With their cargos, mainly consisting of functional proteins, lipids and nucleic acids, they can activate signalling cascades and thus change the phenotype of recipient cells at local and systemic levels. Their substantial role as modulators of various physiological and pathological processes is acknowledged. Importantly, more and more evidence arises that EVs play a pivotal role in many stages of carcinogenesis. Via EV-mediated communication, tumour cells can manipulate cells from host immune system or from the tumour microenvironment, and, ultimately, they promote tumour progression and modulate host immunity towards tumour’s favour. Additionally, the role of EVs in modulating resistance to pharmacological and radiological therapy of many cancer types has become evident lately. Our understanding of EV biology and their role in cancer promotion and drug resistance has evolved considerably in recent years. In this review, we specifically discuss the current knowledge on the association between EVs and gastrointestinal (GI) and liver cancers, including their potential for diagnosis and treatment.

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Circulating exosomal CPNE3 as a diagnostic and prognostic biomarker for colorectal cancer

Cited by 109 publications

References 25 publications

Progress in exosome associated tumor markers and their detection methods

Progress in exosome associated tumor markers and their detection methods

A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

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